Intervention study to improve smoking cessation during hospitalization.

OBJECTIVES: In France, hospitals have been smoke free since February 2007. A period of hospitalization may be a good time to enhance a smoker's motivation to quit. This study aimed to assess whether training medical staff in smoking cessation management might improve the rate of smoking cessation during hospitalization. STUDY DESIGN: Non-randomized intervention study. METHODS: Staff of the participating care units either received (intervention group) or did not receive (control group) training in smoking cessation management. The dependent variable was the proportion of inpatients that continued to smoke before (Period 1) and after (Period 2) the training session. RESULTS: In total, 358 patients were included. In Period 1, 55.6% and 50% of the smokers from the intervention and control groups stopped smoking, respectively; the corresponding rates in Period 2 were 64.3% and 48.1%. In Period 2, 36.4% and 31.8% of the smokers from the intervention and control groups claimed that they had received motivational counselling. In the intervention group, the request rate for nicotine replacement therapy (NRT) was higher (41.7%) compared with the control group (11.1%). In both groups, patients asked for NRT more often (P < 0.001) when they had received motivational counselling. CONCLUSIONS: This study was not able to demonstrate that training medical staff in smoking cessation management has a significant impact on smoking cessation in hospitalized smokers. The delivery of medium-intensity support to all smokers appears to be out of reach of physician/nurse teams. New strategies are needed, including a team specifically dedicated to the problems of addiction.

Efficacy and safety of highly purified, doubly virus-inactivated VWF/FVIII concentrates in inherited von Willebrand's disease: results of an Italian cohort study on 120 patients characterized by bleeding severity score.

The efficacy of highly purified VWF/FVIII concentrates with standardized ristocetin cofactor content (VWF:RCo) has been already proven in patients with von Willebrand's disease (VWD). Aim of this retrospective study is to confirm efficacy and safety of two highly purified, doubly virus-inactivated VWF/FVIII concentrates in a large cohort of patients with VWD who were characterized at enrolment by bleeding severity score. Study drugs Alphanate or Fanhdi were given to 120 cases (51 males, 69 females, median age 50 years, range 6-83 years). Patients had VWD3 (10), VWD2A (19), VWD2B (25), VWD2M (10) and DDAVP-unresponsive VWD1 (56) and a median bleeding severity score of 8 (range 0-27). A total of 114 bleeding episodes in 55 cases and 131 surgical procedures in 85 cases could be analysed. Excellent-good clinical responses were seen in 97% of bleeding episodes and in 99% of surgical procedures. To prevent recurrent gastrointestinal (GI) bleeding, cerebral (CNS) haemorrhage, haemarthroses, urogenital or multisite bleeding in more severe patients, secondary prophylaxis was also carried out in 15 cases with VWD3 (3), VWD2A (3), VWD2B (2), VWD1 (7). A median dose of 42 IU VWF:RCo kg(-1) given every other day or twice a week over a median period of 334 days (range 24-799) prevented bleeding completely in 13 cases and reduced its incidence in the remaining two. These results confirm the efficacy and safety of the study concentrates, not only in the management of bleeding and surgery but also in secondary prophylaxis of severe VWD.

Hemarthrosis as acute presentation of acquired hemophilia in a patient with systemic lupus erythematosus: successful treatment and long-lasting remission.

Hemorrhagic events due to production of antibodies directed against coagulation factors are rarely observed in systemic lupus erythematosus (SLE). We report the case of a patient with clinically quiescent SLE who developed factor VIII inhibitor in acquired hemophilia presenting as hemarthrosis. Initial treatment with FVII, FVIII and FIX plasma concentrate, metilprednisolone and immunoglobulins i.v. were started but new hemorrhagic manifestation occurred. Plasma exchange was also administered, but it was discontinued early due to partial efficacy. In addition, pulse cyclophosphamide 0.5 g/m(2) was started. Eight weeks later, FVIII and FIX activity returned within normal ranges, FVIII and FIX inhibitors decreased significantly and hemorrhagic manifestations disappeared. The rare occurrence of acquired hemophilia due to the presence of anti-factor VIII antibodies associated to SLE, which was reviewed, might explain the lack of therapeutic guide-lines; indeed therapeutic options are available but the outcome in each single patient is not predictable.

Clinical efficacy of highly purified, doubly virus-inactivated factor VIII/von Willebrand factor concentrate (Fanhdi) in the treatment of von Willebrand disease: a retrospective clinical study.

The goal of therapy in patients with von Willebrand disease (vWD) is to correct the dual defect of primary haemostasis and intrinsic coagulation reflected by low levels of von Willebrand factor (vWF) and factor VIII coagulant activity (FVIII:C). Factor VIII/von Willebrand factor (FVIII/vWF) concentrates are currently the treatment of choice in vWD patients unresponsive to desmopressin (DDAVP). However, only few studies on their clinical use are available so far. The main objective of this study was to retrospectively evaluate the clinical efficacy of a highly purified, doubly virus-inactivated FVIII/vWF concentrate with a high content of FVIII/vWF (Fanhdi). Twenty-two patients with congenital vWD have been treated from 1999 to 2001 at eight specialized centres belonging to the Italian Association of Hemophilia Centers (AICE). Ten males and 12 females, median age 28.5 years, range 5-70 years) had type 3 vWD (six cases), DDAVP-unresponsive type 1 (nine cases) and type 2B (seven cases). The study drug was given to stop or prevent 12 bleeding episodes or to prevent excessive bleeding during 14 surgical or invasive procedures. Overall, replacement therapy with the concentrate showed an excellent to good clinical efficacy in 92% of bleeding episodes and in 93% of surgical procedures. No adverse events occurred during 1,601 infusions, accounting for a total of 304,500 IU of FVIII:C administered. These results confirm the efficacy and safety of this concentrate in the management of bleeding episodes and in the prevention of excessive bleeding during major and minor surgery.

Diaphragm kinetics during pneumatic belt respiratory assistance: a sonographic study in Duchenne muscular dystrophy.

The principal aim of this study was to demonstrate the usefulness of M-mode sonography as a noninvasive technique to evaluate diaphragm excursion. The secondary aim was to assess the efficacy of pneumatic abdomino-diaphragmatic belt ventilation in patients with Duchenne muscular dystrophy. Using M-mode sonography, we measured the amplitude of diaphragm excursion in seven patients with Duchenne muscular dystrophy in various positions (0 degrees, 45 degrees, 75 degrees ) with and without pneumatic abdomino-diaphragmatic belt respiratory assistance. The belt significantly increased mean amplitude of diaphragm excursion by 62% at 45 degrees and by 55% at 75 degrees, and increased mean tidal volume by 43.5% at 45 degrees and by 49% at 75 degrees. Two patients were unable to tolerate the horizontal position (0 degrees ) During quiet breathing without the belt, amplitude of diaphragm excursion and tidal volume were positively correlated at 45 degrees (r=0.81; P=0.027) and 75 degrees (r=0.75; P=0.05). There was a significant intra-individual correlation between these two parameters during belt use but no inter-individual correlation. Without the belt, thoracic posture had no significant effect on amplitude of diaphragm excursion, either in quiet or deep breathing. After overnight respiratory assistance, arterial oxygen pressure and arterial oxygen saturation increased significantly, and arterial carbon dioxide pressure decreased from 52+/-6.4 to 46.4+/-4 mmHg. The pneumatic abdomino-diaphragmatic belt significantly improved gas exchanges and ventilation by increasing diaphragm excursion, as was clearly shown by noninvasive M-mode sonography. Indeed, M-mode sonography may be helpful in pneumatic abdomino-diaphragmatic belt pressure adjustment.

Congenital afibrinogenemia: mutations leading to premature termination codons in fibrinogen A alpha-chain gene are not associated with the decay of the mutant mRNAs.

Congenital afibrinogenemia is a rare coagulation disorder with autosomal recessive inheritance, characterized by the complete absence or extremely reduced levels of fibrinogen in patients' plasma and platelets. Eight afibrinogenemic probands, with very low plasma levels of immunoreactive fibrinogen were studied. Sequencing of the fibrinogen gene cluster of each proband disclosed 4 novel point mutations (1914C>G, 1193G>T, 1215delT, and 3075C>T) and 1 already reported (3192C>T). All mutations, localized within the first 4 exons of the A alpha-chain gene, were null mutations predicted to produce severely truncated A alpha-chains because of the presence of premature termination codons. Since premature termination codons are frequently known to affect the metabolism of the corresponding messenger RNAs (mRNAs), the degree of stability of each mutant mRNA was investigated. Cotransfection experiments with plasmids expressing the wild type and each of the mutant A alpha-chains, followed by RNA extraction and semiquantitative reverse-transcriptase-polymerase chain reaction analysis, demonstrated that all the identified null mutations escaped nonsense-mediated mRNA decay. Moreover, ex vivo analysis at the protein level demonstrated that the presence of each mutation was sufficient to abolish fibrinogen secretion.

Cryptococcal meningitis following a thrombotic microangiopathy in an unrelated donor bone marrow transplant recipient.

In patients undergoing bone marrow transplantation cryptococcosis is rarely encountered. We report a fatal case of Cryptococcus meningitis in a 12-year-old girl with acute lymphoblastic leukemia (ALL) in second remission who had a transplant from a human leukocyte antigen (HLA)-identical unrelated bone marrow donor. The conditioning regimen was thiotepa, cyclophosphamide, and total body irradiation (TBI); graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A, methotrexate, and antilymphocyte globulin (ALG). The patient experienced stage III GVHD responsive to high-dose corticosteroids. On day +54 a thrombotic microangiopathy occurred. On day +64 neurological status worsened; a brain computed tomographic (CT) scan showed hyperdense lesions suggesting fungal infection. Detection of cryptococcal antigen by latex agglutination was positive but India ink stain and culture were negative. Despite treatment with amphotericin B, 5-flucytosine, and granulocyte-macrophage colony-stimulating factor, the patient died 13 days after the diagnosis.

Non-invasive quantification of diaphragm kinetics using m-mode sonography.

PURPOSE: The standard conditions of spirometry (i.e., wearing a noseclip and breathing through a mouthpiece and a pneumotachograph) are likely to alter the ventilatory pattern. We used "time motion" mode (M-mode) sonography to assess the changes in diaphragm kinetics induced by spirometry during quiet breathing. METHODS: An M-mode sonographic study of the right diaphragm was performed before and during standard spirometry in eight patients without respiratory disease (age 34 to 68 yr). RESULTS: During spirometry, the diaphragm inspiratory amplitude (DIA) increased from 1.34 +/- 0.18 cm to 1.80 +/- 0.18 cm (P = 0.007), whereas the diaphragmatic inspiratory (T1 diaph) increased from 1.27 +/- 0.15 to 1.53 +/- 0.23 sec, (P = 0.015, without change in diaphragmatic total time interval (Ttot diaph). Therefore, the diaphragm duty cycle (T1 diaph/Ttot diaph) increased from 38% +/- 1% to 44% +/- 4% (P = 0.023). The diaphragm inspiratory (DIV) and expiratory (DEV) motion velocity (P = 0.007). CONCLUSION: M-mode sonography enabled us to demonstrate that the wearing of a nose clip and breathing through a mouthpiece and a pneumotachograph induce measurable changes in diaphragm kinetics.

Pulmonary gas exchange capacity is reduced during normovolaemic haemodilution in healthy human subjects.

PURPOSE: To test the hypothesis that a physiological compensatory mechanism maintains respiratory gas exchange during normovolaemic haemodilution. METHODS: Pulmonary gas exchange capacity was evaluated in seven healthy subjects by measuring the lung diffusion of carbon monoxide (DLCO). During the measurement, various breath-holding times, inspiratory volumes, and sitting or supine positions, were randomly selected in an attempt to alter pulmonary capillary perfusion. KCO was calculated as the percentage of theoretical values of the ratio of DLCO by alveolar volume and normalized by sex, age, and height. Normovolaemic haemodilution (NH) was performed by bleeding an average blood volume of 1 L with simultaneous Dextran 60 replacement to obtain an haematocrit below 35%. RESULTS: After NH, haemoblogin concentration [Hb] decreased from 14.94 +/- 0.96 to 12.5 +/- 0.98 g.dl-1 (P < 0.001). KCO decreased (P < 0.02) but remained closely correlated to [Hb] at every lung volume (P < 0.02). Breathholding time and body position had no effect. CONCLUSION: Moderate NH impairs pulmonary gas exchange capacity in awake, resting healthy subjects. There is no evidence of any compensatory mechanism since the KCO vs [Hb] relationship is unchanged.

Analysis of risk factors in a cluster of childhood acute lymphoblastic leukemia.

A case-control investigation of childhood acute lymphoblastic leukemia was conducted in the town of Carbonia (Sardinia, Italy). Parents of 9 cases diagnosed between 1980 and 1989 and 36 controls were interviewed at their respective residences. None of the risk factors analyzed was associated significantly with childhood acute lymphoblastic leukemia. The following were associated with an increased risk for childhood acute lymphoblastic leukemia: parents born outside of Carbonia, family history of cancer, alcohol consumption by fathers that exceeded 60 g/d, exposure of fathers to solvents at their workplaces, maternal smoking, use of antinausea medications during pregnancy, and presence of a well in the backyard. Chance and recall bias likely played a role in generating positive associations. The increases in childhood leukemia risk associated with the presence of a well and with use of antinausea medications during pregnancy are consistent with previous reports and require further investigation.

Childhood Acute Lymphoblastic Leukemia: A Cluster in Southwestern Sardinia (Italy).

In response to public concern about an increase in the incidence of leukemia among children in southwestern Sardinia (Italy), incident cases of childhood cancer (ages 0-14) were ascertained among residents in the province of Cagliari, which comprises all of southern Sardinia, in 1974-89. Completeness of the ascertainment of leukemia cases was validated by comparison with estimates derived from official statistics of mortality and survival curves. A significant excess risk of childhood acute lymphoblastic leukemia (cALL) was found for children residing in the town of Carbonia. The risk was highest in 1983-85, when seven cases occurred versus 0.8 expected. No birth-cohort effect was observed. The cALL incidence rate was significantly higher among children born and residing in Carbonia than among children born in Carbonia but residing elsewhere. However, the cALL cases did not cluster within the town of Carbonia. The proximity of the largest industrial settlement in the region of Sardinia raised the suspicion that environmental pollution was responsible for the observed excess. Information about industrial emissions from this settlement prior to the appearance of the cALL cluster was not sufficient to reject or confirm the hypothesis.

[Right diaphragmatic kinetics measured by TM-mode ultrasonography with concomitant spirometry in normal subjects and asthmatic patients. Preliminary results]. / Cinétique diaphragmatique droite mesurée par ultrasonographie en mode TM avec spirométrie concomitante chez le sujet normal et asthmatique. Résultats préliminaires.

The purpose of this study was to assess the diaphragmatic excursion using the TM-mode ultrasonography with concomitant pneumotachography in eight normal and five asthmatic subjects before and after salbutamol. We report the results in normal and asthmatic patients of this procedure. Particular findings were demonstrated in asthma. Different significant correlations were found between sonographic and respiratory measurements. In view of the safety of this direct and real-time diaphragmatic investigation, we conclude that this new method could offer an effective and reliable procedure in the evaluation of patients with diaphragmatic dysfunction. However, our study was limited by the small number of patients included and definite conclusions should await further investigations.

Sonographic lung surface evaluation in pulmonary sarcoidosis: preliminary results.

The value of sonography in lung diseases such as sarcoidosis is not established. Twelve patients with pulmonary sarcoidosis and eight control subjects underwent a sonographic examination using a high frequency probe (7.5 MHz). The normal lung surface showed smooth and regular hyperechoic patterns, respiratory motions, and occasionally minute interruptions with comet tails. All patients with sarcoidosis showed various surface abnormalities, which appeared irregular and rough with coarse interruptions, producing an increase of artifacts. Nodular patterns were found in nine of 12 patients (75%). Sonography also revealed abnormalities not diagnosed by chest radiographs (n = 2). These findings could offer an complementary approach for evaluating sarcoidosis.

Childhood leukemia in south-west Sardinia (Italy).

AIM AND BACKGROUND: Public concern on an increased incidence of childhood leukemia in SW Sardinia prompted the authors to an epidemiological investigation. METHODS: Incident childhood neoplasms observed in the Cagliari province (Sardinia--Italy) in 1974-1989 were registered. Expected cases of the most frequent childhood cancers were calculated for each town, based on the sex-and age-specific incidence rates in the province. RESULTS: An excess risk of childhood acute lymphoblastic leukemia (ALL) was observed in Carbonia, a town located in the SW part of the province. The risk was highest in 1983-85, when 7 cases occurred versus 0.8 expected (RR = 8.7; 95% C.I. = 4.6, 16.3). No spatial clustering of ALL cases was observed within the town. CONCLUSIONS: A significantly higher than expected incidence of childhood ALL was observed in the town of Carbonia in 1983-85. In alternative to chance, possible exposure to environmental pollutants from a near industrial settlement is discussed as the cause of the observed excess, but it is far to be proven. Other hypotheses, including a viral infection in a population with increased susceptibility, as suggested for new urban settlements, cannot be discarded.

Peripheral pulmonary lesions: ultrasonic features and ultrasonically guided fine needle aspiration biopsy.

When transthoracic biopsy is required for diagnosing lung diseases, radiographic procedures are the methods of choice, sonographic application being still limited. Sixty-four consecutive patients with pulmonary lesions adjacent to the chest wall underwent sonography. Findings showed hypoechoic homogeneous lesions (56 cases) with posterior regular margin (57 cases). Increasing echoes deep to the mass and sonographic interruption of hyperechoic surface were seen in all patients. In two cases, chest wall invasion had been diagnosed. Histologic diagnosis was made in 55 of the 64 patients (85.9%). Two pneumothoraces occurred. Sonography is a useful, accurate, and safe technique for diagnosing selected pulmonary lesions.

Ultrasonically guided aspiration biopsy in osteolytic bone lesions of the chest wall.

Sixteen consecutive patients with one or more osteolytic bone lesions of the chest wall radiologically confirmed underwent ultrasonically guided aspiration biopsy. Nine patients (56.2 percent) had bronchogenic carcinoma with a direct extension. Other diagnostic techniques had failed to diagnose disease in these patients. The lesion showed heterogeneous echogenicity (n = 16) caused by the hyperechoic signals of bone fragments. The interruption of the cortex bone was detected in all cases and extraosseous tumor portion in 14 of 16 patients (87.5 percent). No respiratory motions of the lesion could be demonstrated (n = 16). Definitive histologic diagnosis was made in 14 of the 16 patients (87.5 percent). In malignancy, diagnosis was established in 13 of 14 patients (92.8 percent). Of two confirmed benign lesions, one diagnosis of tuberculosis was obtained. No complication occurred. Sonography and consequently ultrasonically guided aspiration biopsy are a useful, accurate, safe, and low-cost technique for osteolytic lesions in thoracic diseases.

Ultrasonic signs of pneumothorax: preliminary work.

Ultrasonography is considered to have limited application in respiratory diseases because air reflects sound waves. Twenty-four patients with radiologically confirmed pneumothorax and 100 healthy subjects underwent sonography. In all normal subjects, the hyperechoic pulmonary interface showed respiratory motions termed the "gliding sign" with some comet-tail artifacts. Sonographic signs were shown in all pneumothoraces: disappearance of the gliding sign and no comet tails. The extent of collapse cannot be evaluated, but it is possible to determine its area in partial pneumothorax (N = 5). The follow-up (N = 8) showed the reappearance of the gliding sign. Ultrasonography may be helpful in diagnosing pneumothorax in certain cases.